Preparation and Biocompatibility Evaluation of Nanoscale Isoniazide-Loaded Mineralized Collagen Implants for Tuberculous Bone and Joint Repair.

Bone and joint tuberculosis is an extremely severe infectious disease that commonly occurs due to the primary infection of a type of mycobacteria, called Mycobacterium tuberculosis. Under the current scenario, there are very limited supplies of bone grafts available for the treatment of deceased bone, including autogenous bone and synthetic biomaterials. The present study aimed to construct a nanoscale isoniazid-loaded mineralized collagen implant, and then to explore its physicochemical properties and to investigate its biocompatibility suitable for bone and joint repair. Using type I collagen as raw material and the principle of biomimetic mineralization for self-assembly of bone tissue, a new drug-loaded mineralized collagen implant was constructed by molecular coprecipitation with isoniazid. Its surface morphology, elemental composition, and porosity were characterized by field emission scanning electron microscope (SEM), X-ray diffraction (XRD), and pycnometer. The performance of the implant was gauged by sustained release and degradation, which were studied using an ultraviolet spectrophotometer and a simulated in vivo environment. The drug loading and encapsulation rates of the implants were (6.25 ± 0.48)% and (54 ± 2.34)%, respectively. The in vitro release time of the scaffold was more than 12 weeks and the degradation performance was excellent. The scaffold was then implanted into mice, and the inflammatory reaction of local tissue was observed by Haemotoxylin and Eosin (H&E) and Masson. The in vivo evaluation in mice showed that the scaffold was biocompatible. Overall, compared with traditional drug loading systems, the isoniazid biomimetic mineralized collagen implant constructed here has better drug release performance, biodegradability, and biocompatibility. This kind of collagen implant may find potential applications in tuberculous bone and joint repair.

A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome.

BACKGROUND: Mesenchymal stromal cell conditioned medium (MSC-CM) contains a cocktail of bioactive factors that act synergistically to induce therapeutic effects. This has been clearly demonstrated by in vivo applications of MSC-CM, but the establishment of controlled delivery systems is an unmet requirement for clinical translation. METHODS: We developed a nanocomposite-hydrogel (NP-H) comprised of poly-L-lactide nanoparticles (NPs) embedded in gelatin/hyaluronic acid (Gel/HA) hydrogel as a delivery vehicle for MSC-CM. First, we optimized the culture conditions for bone marrow-derived MSCs using serum-containing medium (SCM) and serum-free medium (SFM) and characterized the corresponding CM (serum-containing conditioned medium (ScCM) and serum-free conditioned medium (SfCM), respectively) for its potency and xeno markers. Then we prepared a composite matrix followed by physiochemical characterization and functional assays were performed. RESULTS: Nanocomposite hydrogel displayed an even distribution of NPs along with high porosity (> 60%) and swelling ratios > 1500%, while its protein release pattern corresponded to a mix of degradation and diffusion kinetics. Functional evaluation of the composites was determined using MSCs and human fibroblasts (HFFs). The cells seeded directly onto the composites displayed increasing metabolic activities over time, with ScCM-NP-H groups having maximum activity. The cells treated in vitro with 5% and 10% extracts of ScCM-NP-H and SfCM-NP-H exhibited a dose- and duration-dependent response. Cell activities reduced considerably for all groups, except 10% ScCM-NP-H, which displayed a significant increase over time. CONCLUSION: We observed that sustained release of MSC-CM is required to prevent dose-dependent cytotoxicity. The proposed nanocomposite hydrogel for MSC-CM delivery can open up a new array for its clinical application.